遗传学与分子生物学系

遗传学与分子生物学系MolucularBiologyLuShermin(吕社民)Tel:[phone]Email:[e-mail]遗传学与分子生物学系LectureI:IntroductionOfMolecularBiology1.Definition,GoalandScope2.Fundamentals3.Abriefhistory4.MethodologyofMolecularBiology5.RoleinMedicalsciences6.prospective遗传学与分子生物学系Definition•Anelusiveterm,MorethanonedefinitionStudylife(biology)inmolecularlevelStudygenestructureandfunctionatthemolecularlevel.Grewoutofthedisciplinesofgeneticsandbiochemistry.•HybriddisciplineBiochemistryGeneticsMolecularBiologyBiophysics遗传学与分子生物学系GoalTounderstandthefivebasiccellbehaviorpatterns(growth,division,specialization,movement,andinteraction)intermsofvariousmoleculesthatareresponsibleforthem遗传学与分子生物学系Scope•StructureandfunctionofNucleotidesandprotein•Structureandfunctionofgenome•Geneproliferation,expression,regulationandbiologicalfunction•Interactionbetweenbiologicalmacromolecules•Intraandintermolecularsignaltransduction•Technologyofmolecularbiology遗传学与分子生物学系ScopeofMedicalMolecularBiology•Molecularmechanismofcellulargrowth,differentiationandSenescenceinhumanbeing•Molecularbasisofproliferationanditsregulationofhumancells•MolecularBiologyofthreeregulatorysystems(nervous,endocrineandimmunesystems)inhumanbody•Relationshipbetweenabnormalityofgenestructure,regulationwithetiopathogenesisofhumandiseases•Genediagnosisandgenetherapyintermsoftheoryandtechnologyofmolecularbiology•Drugdiscoveryandhealthcareintermsoftheoryandtechnologyofmolecularbiology遗传学与分子生物学系LectureI:IntroductionOfMolecularBiology1.Definition,GoalandScope2.Fundamentals3.Abriefhistory4.MethodologyofMolecularBiology5.RoleinMedicalsciences6.prospective遗传学与分子生物学系遗传学与分子生物学系“Weak”Interactions•Chemicalbonds(covalent)haveenergiesof~101-2kcal/mole.STRONG•Weakinteractions–Hydrogenbonds~5kcal/mole–VanderWaalsinteractions~1kcal/mole•“Hydrophobic”interactions–Lessclassifiable,aconsequenceofotherforces遗传学与分子生物学系Hydrophobicinteractions•Polarmaterials(water)onbalancehaveattractiveintermolecularforces.•Nonpolarmaterialshavenoparticulartendencytoassociate.–Result:Nonpolarmaterialswithinanaqueouscompartmentassociatebecausetheyareexcludedbythemutuallyattractiveforcesbetweenthemoleculesofthemedium遗传学与分子生物学系Nucleotides•Base•Sugar(Base+Sugar=Nucleoside)•Phosphate(Nucleoside+phosphate=Nucleotide)遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系遗传学与分子生物学系LectureI:IntroductionOfMolecularBiology1.Definition,GoalandScope2.Fundamentals3.Abriefhistory4.MethodologyofMolecularBiology5.RoleinMedicalsciences6.prospectiveGregorMendel(1822-1884)MAURICEH.F.WILKINS(1916-)ROSALINDE.FRANKLIN(1920-1958)LinusCarlPauling(1901-1994)OswaldTheodoreAvery(1877-1955)遗传学与分子生物学系Abriefhistory(timeline)1839Schleiden&SchwannCelltheory1859Darwin:OriginofSpecies1865Mendel:Genetics1869Miescher:discoveredDNA1902SuttenChromosome1910,1916Morgan:geneareonchromosomes1944Avery:identifiedDNAasthematerialgenesaremadeof1953WatsonCrick：DNAstructure1958Meselson&Stahl:semiconservativereplicationofDNA1961Jacobetal:discoveredmRNA1972Berg:recombinantDNAinvitro1973Cohen:firstusedplasmidtocloneDNA1977Gilbert&Sanger:sequence1986Mullis:PCR1990Watsonetal:LauchedtheHGP1997Wilmut:Dolly1998-Bioinformatics,Proteomes(ome)遗传学与分子生物学系MajorAchievementsofMolecularBiologyafter70s•DNApolymerasedependentonRNA(Reversetranscription)•Toolenzymes(restrictiveendonuclease,DNAligase,etc)•Splitgene•DNASequencing•MAb•Ribozymes•PCR•Generegulation•Transgenicorganism•DNArecombinationinintroandinvivo(genetherapy)•HGP•iRNA•Proteomics•Hapmap(SNPs)•Bioinformatics•Systemsbiology遗传学与分子生物学系LectureI:IntroductionOfMolecularBiology1.Definition,GoalandScope2.Fundamentals3.Abriefhistory4.MethodologyofMolecularBiology5.RoleinMedicalsciences6.prospective遗传学与分子生物学系Physicalandchemicalapproaches_________________________________________________________Ultracentrifuge*20sSizeandshapeofmoleculeincentrifugalfieldElectrophoresis*30sseparationofproteinandnucleicacidsbasedonsizeand/orchargeinelectricfieldElectronMicroscope30sdirectlyvisualizationofcellarultra-structure,includingDNARadioisotopetracers*40strackingflowofmoleculethroughametabolicpathwayX-raydiffraction*50sprovidesprecisemeasurementof3-DstructureofproteinandnucleicacidAminoacidanalysis*50sdeterminationoforderofaminoacidinproteinNucleicacidhybridization60squantitativeassessmentofsimilarityofRNAsorDNAsRecombinantDNA*70sgeneticengineeringofnovelgenes------------------------------------------------------------------------------------------------*DenotesassociatedwithNobelPrize遗传学与分子生物学系GeneticMethodsMutantorganisms•recoginizeaNovelprocess•unravelacomlexmetabolicpathway•establisharelationshipbetweenanidentifiedgeneanditspreviousunknownfunctionPuregenes•pin-pointsubstitutionordeletion•reversegenetics遗传学与分子生物学系ModelBiologicalsystemVirusBacteriaBacteriophageYeastWorm(C.elegant)Plant(Arabidopsis)FlyMouseRathuman遗传学与分子生物学系Logicofmolecularbiology•Theefficiencyargument•Phylogenetichistory•Quantitativeassessment•Modelbuilding•Parallelism•Stronginference•Optimism遗传学与分子生物学系LectureI:IntroductionOfMolecularBiology1.Definition